Posted by Graham McMahon • April 2nd, 2010

Andriole et al. tested dutasteride, an inhibitor of 5-reductase in the prostate, in a large, randomized trial to determine its abilityto prevent prostate cancer. Over the 4 years of the trial, dutasteride,as compared with placebo, reduced the relative risk of biopsy-detectedprostate cancer by 23%. The reduction was limited mainly totumors with Gleason scores of 5 or 6; by year 4, there were12 tumors with Gleason scores of 8 to 10 in the dutasteridegroup but only 1 in the placebo group.

The 5(alpha)-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and may reduce the risk of prostate cancer. The results of the Prostate Cancer Prevention Trial showed that finasteride, as compared with placebo, reduced the risk of prostate cancer by 25%, but among the tumors that were detected, there was a 27% increase in the number of those that had Gleason scores of 7 to 10.

Clinical Pearls

• What is the mechanism of action of dutasteride?

There are two isoforms of 5(alpha)-reductase, type 1 and type 2. Expression of type 1 in the prostate is enhanced during the development of prostate cancer, whereas the expression of type 2 is decreased or unchanged. Unlike finasteride, dutasteride inhibits both isoforms of 5(alpha)-reductase.

• How did treatment with dutasteride improve symptoms related to benign prostatic hyperplasia?

During the 4 years of the study, 659 of the 3305 men in the dutasteride group (19.9%) and 858 of the 3424 men in the placebo group (25.1%) received a diagnosis of prostate cancer, representing an absolute risk reduction with dutasteride of 5.1 percentage points.

Morning Report Questions

Q: What adverse effects of dutasteride were noted in this study?

A: A drug-related decrease in libido was reported by 3.3% of the men in the dutasteride group, as compared with 1.6% of the men in the placebo group, and a loss of libido was reported by 1.9% of the men in the dutasteride group, as compared with 1.3% of the men in the placebo group (P<0.05 for both comparisons). A drug-related decrease in or loss of erectile function was reported in 9.0% of the men in the dutasteride group and in 5.7% of the men in the placebo group (P<0.05).

Q: How did treatment with dutasteride affect the pathologic end points?

A: Over the 4 years of the study, there were 437 tumors with Gleason scores of 5 to 6 in the dutasteride group and 617 in the placebo group (P<0.001), and such tumors accounted for 70% of the total number of cancers. The number of tumors with Gleason scores of 7 to 10 did not differ significantly between the dutasteride group and the placebo group (220 and 233, respectively; P=0.81). There were 29 tumors with Gleason scores of 8 to 10 in the dutasteride group and 19 in the placebo group (P=0.15).

Table 2. Incidence of Prostate Cancer and Relative Risk Reduction over the Course of the 4-Year Study Period, According to Baseline Subgroups.